As noted by Sullivan in U.S. Pat. No. 5,620,921 (Sullivan '921), “The preocular tear film plays an important role in the maintenance of corneal integrity, the protection against infection and the preservation of visual acuity.” A healthy tear film preserves the optical clarity and refractive power, provides lubrication of the ocular surface and protection from environmental and infectious attacks. Sullivan '921 further notes that “These functions, in turn, are critically dependent upon the stability, tonicity and/or composition of the tear film structure. Healthy tears contain a complex mixture of proteins such as antimicrobial proteins (lysozyme, lactoferrin) and growth factors and inflammation suppressors, mucin which provides viscosity and stability of the tear and electrolytes for proper osmolarity. Alteration, deficiency or absence of the tear film may lead to undesired dryness of the corneal epithelium, ulceration and perforation of the cornea, an increased incidence of infectious disease, and ultimately, severe visual impairment and blindness.” (See Sullivan '921 at col. 1, lines 19-30.)
The condition of dry eye is often referred to as a syndrome, or a disease; and it is likewise known by a variety of terms. Keratoconjunctivitis sicca (KCS), or more commonly keratitis sicca, refers to any eye with some degree of dryness.
In dry eye the eye becomes dry either because there is abnormally high rate of evaporation of tears or because there is not enough tears being produced. The contents of the tear in an eye suffering from dry eye are altered with lesser concentrations of proteins such as cytokine which promotes inflammation. Additionally, soluble mucin is greatly decreased due to loss of goblet cells which impacts viscosity of the tear film. Moreover, there is an increase in electrolyte concentration.
Throughout the world, countless individuals suffer from dry eye syndrome. The abnormalities leading to tear film dysfunction may be subdivided into four general categories: (a) aqueous tear deficiencies, which are most frequently responsible for dry eye states, originate from lacrimal gland disorders and include autoimmune disease, congenital alacrima, paralytic hyposecretion or excretory duct obstruction; (b) mucin deficiency, which is observed in various conjunctival cicatrization conditions, such as Stevens-Johnson syndrome, trachoma, pemphigoid, thermal and chemical burns, as well as hypovitaminosis A; (c) lipid abnormalities, which may occur during eyelid inflammation (e.g. chronic blepharitis); and (d) diminished eyelid function [Holly, F. J., Tear film physiology. Internat. Ophthalmol. Clin. 27:2-6 (1987)].
The first line of treatment is usually eye drops, preferably preservative free, that act as artificial tears. Most artificial tears are hydrogels that increase the moisture content on the eye surface and give some temporary relief. These solutions and ointments give some temporary relief, but do little to arrest or reverse any damaging conditions. A recently introduced artificial tear product is based on Castor oil emulsion (Refresh Endura tears).
In addition, warm moist compresses applied to the skin of the closed eyelids are also used to reduce tear loss due to evaporation.
For more severe cases of dry eye, in which the cornea is inflamed, anti-inflammatory agents, such as topical steroids (in eye drops) are sometimes prescribed. One example includes the combination of castor oil with cyclosporine (Restasis).
Oral medicine for dry eye is also available. For example, pilocarpine, the active ingredient in Salagen™ or cevimeline, the active ingredient in Evoxac™, are known to stimulate specific receptors in lacrimal gland and cause increased secretion of tears.
Other remedies include punctal plugs and punctal closure (which block the tears from flowing down the tear duct into the nose), and food supplements, such as the commercially available Flaxseed oil supplement (Omega-3 Supplement, TheraTears).
Adenosine receptors are classified into four major classes: A1, A2a, A2b and A3. A3 adenosine receptors belong to the family of the Gi-protein associated cell surface receptors. Receptor activation leads to its internalization and the subsequent inhibition of adenylyl cyclase activity, cAMP formation and protein kinase A (PKA) expression, resulting in the initiation of various signaling pathways. PKA contains a catalytic subunit PKAc which dissociates from the parent molecule upon activation with cAMP.